ArticleApplied and environmental microbiology2005
Metabolic engineering of the purine pathway for riboflavin production in Ashbya gossypii.
Article in Applied and environmental microbiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 134 citations in OpenAlex.
- Biosynthesis, Regulation, and Biotechnological Production Strategies of Riboflavin (Vitamin BPharmaceuticals (Basel, Switzerland) · 2026Review
- Scarless Genetic Engineering ofJournal of microbiology and biotechnology · 2025Article
- Regulation of Riboflavin Biosynthesis in Microorganisms and Construction of the Advanced Overproducers of This Vitamin.International journal of molecular sciences · 2025Review
- Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast.PLoS biology · 2025Article
- Ashbya gossypii as a versatile platform to produce sabinene from agro-industrial wastes.Fungal biology and biotechnology · 2024Article
- Regulatory Functions of PurR inMicroorganisms · 2023Article
- Metabolic Engineering ofMicroorganisms · 2023Review
- Effects of alcohol on the symptoms of gouty arthritis and taxonomic structure of gut microbiota in C57BL/6 mice.Frontiers in microbiology · 2023Article
- In silico-guided metabolic engineering of Bacillus subtilis for efficient biosynthesis of purine nucleosides by blocking the key backflow nodes.Biotechnology for biofuels and bioproducts · 2022Article
- Metabolic engineering of Ashbya gossypii for limonene production from xylose.Biotechnology for biofuels and bioproducts · 2022Article
- Enhancing the biosynthesis of riboflavin in the recombinantFrontiers in microbiology · 2022Article
- New Promoters for Metabolic Engineering ofJournal of fungi (Basel, Switzerland) · 2021Article
- Effects of sirtuins on the riboflavin production in Ashbya gossypii.Applied microbiology and biotechnology · 2021Article
- Sugar transport for enhanced xylose utilization in Ashbya gossypii.Journal of industrial microbiology & biotechnology · 2020Article
- Genomic Edition ofBio-protocol · 2020Article
- Genomic analysis of a riboflavin-overproducing Ashbya gossypii mutant isolated by disparity mutagenesis.BMC genomics · 2020Article
- Production of riboflavin and related cofactors by biotechnological processes.Microbial cell factories · 2020Review
- Production of Vitamin B2 (Riboflavin) by Microorganisms: An Overview.Frontiers in bioengineering and biotechnology · 2020Review
- One-vector CRISPR/Cas9 genome engineering of the industrial fungus Ashbya gossypii.Microbial biotechnology · 2019Article
- Metabolic flux analysis in Ashbya gossypii usingMicrobial cell factories · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purine nucleotides are essential precursors for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and the biosynthesis of several amino acids and vitamins such as riboflavin. GTP is the immediate precursor for riboflavin biosynthesis, and its formation through the purine pathway is subject to several regulatory mechanisms in different steps. Extracellular purines repress the transcription of most genes required for de novo ATP and GTP synthesis. Additionally, three enzymes of the pathway, phosphoribosyl pyrophosphate (PRPP) amidotransferase, adenylosuccinate synthetase, and IMP dehydrogenase, are subject to feedback inhibition by their end products. Here we report the characterization and manipulation of the committed step in the purine pathway of the riboflavin overproducer Ashbya gossypii. We report that phosphoribosylamine biosynthesis in A. gossypii is negatively regulated at the transcriptional level by extracellular adenine. Furthermore, we show that ATP and GTP exert a strong inhibitory effect on the PRPP amidotransferase from A. gossypii. We constitutively overexpressed the AgADE4 gene encoding PRPP amidotransferase in A. gossypii, thereby abolishing the adenine-mediated transcriptional repression. In addition, we replaced the corresponding residues (aspartic acid310, lysine333, and alanine417) that have been described to be important for PRPP amidotransferase feedback inhibition in other organisms by site-directed mutagenesis. With these manipulations, we managed to enhance metabolic flow through the purine pathway and to increase the production of riboflavin in the triple mutant strain 10-fold (228 mg/liter).
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